Progesterone regulates lipid synthesis and secretion in bovine uterine epithelial cells

Abstract Uterine secretions consist of a mixture of nutrients that support the growth of the implanted embryo. Our previous data showed that progesterone increased NADPH production in bovine uterine epithelial (BUTE) cells, leading us to hypothesize that progesterone modulates lipid synthesis and secretion. R. Untargeted lipidomics of control and progesterone-treated (10 μM) BUTE cells and conditioned media detected 1,607 lipid species across 14 distinct lipid subclasses. In conditioned media, progesterone significantly decreased 3 lipid species. Conversely, progesterone increased the levels of 130 lipid species, increasing the concentrations of phosphatidylcholines, oxidized triglycerides, and ether triglycerides. Unbiased lipid clustering analysis in the BUTE cells showed that progesterone produced widespread lipid alterations, significantly increasing 34 and decreasing 19 lipid species. This was validated in BUTE cells in vitro, whereby progesterone increased intracellular triglyceride levels and lipid droplets. Immunohistochemistry of endometrial biopsies collected from the cow uterus on days 1 and 11 of the cycle showed that the lipid storage and esterification enzymes LPIN1 and DGAT2 were significantly higher in the glandular epithelium on day 11. These results suggest that progesterone increases lipid synthesis and secretion by the uterine epithelium when progesterone concentrations are high, such as in the luteal phase or early pregnancy.